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01-01-2013 | Original Article

Phase I trial of exemestane in combination with metformin and rosiglitazone in nondiabetic obese postmenopausal women with hormone receptor–positive metastatic breast cancer

Authors: Francisco J. Esteva, Stacy L. Moulder, Ana M. Gonzalez-Angulo, Joe Ensor, James L. Murray, Marjorie C. Green, Kimberly B. Koenig, Mong-Hong Lee, Gabriel N. Hortobagyi, Sai-Ching Yeung

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2013

Abstract

Purpose

Obese women with breast cancer have worse prognosis than women with normal body mass index. Endocrine therapy resistance is in part mediated by insulin resistance in obese women with breast cancer. We investigated the tolerability and pharmacokinetics of exemestane in combination with metformin and rosiglitazone in nondiabetic overweight and obese postmenopausal women with hormone receptor–positive metastatic breast cancer.

Methods

Patients had previously received chemotherapy and endocrine therapy for breast cancer. Exemestane was given as 25 mg orally per day. Metformin (M) and rosiglitazone (R) were given twice daily. Dose level 1 consisted of M 1,500 mg/day and R 6 mg/day. Dose level 2 consisted of M 2,000 mg/day and R 8 mg/day. Plasma concentrations of exemestane were measured on days 1, 8, and 15.

Results

Twenty patients were enrolled. Fourteen patients received exemestane, metformin, and rosiglitazone. Six patients received exemestane with metformin only (2,000 mg/day). Both regimens were well tolerated at the highest doses tested, and there were no notable changes in plasma exemestane levels. Six patients (30 %) had stable disease for 6 months or longer.

Conclusions

Oral daily administration of exemestane (25 mg) and metformin (2,000 mg) with and without rosiglitazone (8 mg) daily was well tolerated. Exemestane pharmacokinetics were not altered by metformin and rosiglitazone.

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Title: Phase I trial of exemestane in combination with metformin and rosiglitazone in nondiabetic obese postmenopausal women with hormone receptor–positive metastatic breast cancer
Authors: Francisco J. Esteva
Stacy L. Moulder
Ana M. Gonzalez-Angulo
Joe Ensor
James L. Murray
Marjorie C. Green
Kimberly B. Koenig
Mong-Hong Lee
Gabriel N. Hortobagyi
Sai-Ching Yeung
Publication date: 01-01-2013
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2013
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-012-1977-9

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